This proposal describes the renewal of the New England Huntington's Disease Center Without Walls. The objective of this proposal is to continue clinical and basic research directed toward an understanding of an autosomal dominant disorder which serves as an important model of regional programmed nerve cell death. It is proposed to continue to collect data on the pedigrees, clinical findings and autopsy observations of patients seen in the New England area. Medical clinics at the Massachusetts General Hospital and Boston University School of Medicine, together with chronic care facilities at local V.A. Hospitals (West Roxbury and Brockton) and the Middlesex Community Hospital will function to collect neurological, genetic, neuropsychological and epidemiological data. Other projects described in this proposal include: continued work to develop additional probes located close to the Huntington's Disease gene on chromosome 4 and to develop strategies to find and clone the defective gene as outlined by Dr. James Gusella; further studies on the neuropathology of Huntington's Disease described by E.P. Richardson, M.D. using material obtained and stored in the McLean Hospital Brain Tissue Bank; investigations of the function of somatostatin and other neuropeptides in the basal ganglia as described in the proposal by Joseph Martin and Flint Beal; studies on the anatomy and function of the basal ganglia as outlined by Marion DiFiglia; studies on neurotransmitter and neuropeptide receptors using new approaches to the identification and characterization of these receptors as described by Linda Chun and Ann Graybiel. These research efforts of the Center Without Walls are coordinated through an executive committee responsible for the activities of the Center. Important research advances accomplished over the last four years are anticipated to continue during the period for which funding is requested.